IBT-V02 – Multivalent toxoid vaccine against Staphylococcus aureus infections

Rationally designed 5-component toxoid vaccine against pore-forming toxins and superantigens for prevention of S. aureus skin and skin structure infections (SSSI)

IBT-V02 is a multivalent toxoid vaccine indicated for prevention of recurrent skin infections caused by Staphylococcus aureus. IBT-V02 is the only entirely toxoid vaccine for S. aureus currently under development. IBT-V02 is being developed under a grant from CARB-X and NIAID and funding from Novo Holdings. The vaccine is scheduled to enter phase I safety and immunogenicity trial in 2023. IBT-V02 differentiates from other prior efforts for S. aureus vaccine in multiple ways.

• ● Differentiator- Mechanism of Action: The toxoid vaccine is unique as it circumvents the problem that have plagued previous S. aureus candidate vaccine candidates, all of which targeted the surface of S. aureus. Animal studies and evidence from clinic indicate that targeting the surface of S. aureus can lead to a deleterious immune response while toxoid vaccines are protective.
• ● Differentiator- Supported by clinical ad epidemiological evidence: IBT-V02 is the only S. aureus candidate heavily supported by clinical and epidemiological evidence. Previous vaccine efforts relied on very limited efficacy studies in mice.
• ● Differentiator- Animal efficacy: IBT-V02 has demonstrated remarkable efficacy in eight different animal models in mice and rabbits.

Related publications:

Karauzum H, Venkatasubramaniam A, Adhikari RP, Kort T, Holtsberg FW, Mukherjee I, Mednikov M, Ortines R, Nguyen NTQ, Doan TMN, Diep BA, Lee JC, Aman MJ. IBT-V02: A Multicomponent Toxoid Vaccine Protects Against Primary and Secondary Skin Infections Caused by Staphylococcus aureus. Front Immunol. 2021 Mar 10;12:624310. doi: 10.3389/fimmu.2021.624310. PMID: 33777005; PMCID: PMC7987673.

https://pubmed.ncbi.nlm.nih.gov/33777005/

Venkatasubramaniam A, Liao G, Cho E, Adhikari RP, Kort T, Holtsberg FW, Elsass KE, Kobs DJ, Rudge TL Jr, Kauffman KD, Lora NE, Barber DL, Aman MJ, Karauzum H. Safety and Immunogenicity of a 4-Component Toxoid-Based Staphylococcus aureus Vaccine in Rhesus Macaques. Front Immunol. 2021 Feb 25;12:621754. doi: 10.3389/fimmu.2021.621754. PMID: 33717122; PMCID: PMC7947289. Kailasan S, Kort T, Mukherjee I, Liao GC, Kanipakala T, Williston N, Ganjbaksh N, Venkatasubramaniam A, Holtsberg FW, Karauzum H, Adhikari RP, Aman MJ. Rational Design of Toxoid Vaccine Candidates for Staphylococcus aureus Leukocidin AB (LukAB). Toxins (Basel). 2019 Jun 14;11(6):339. doi: 10.3390/toxins11060339. PMID: 31207937; PMCID: PMC6628420.

https://www.frontiersin.org/articles/10.3389/fimmu.2021.621754/full

Venkatasubramaniam A, Adhikari RP, Kort T, Liao GC, Conley S, Abaandou L, Kailasan S, Onodera Y, Krishnan S, Djagbare DM, Holtsberg FW, Karauzum H, Aman MJ. TBA225, a fusion toxoid vaccine for protection and broad neutralization of staphylococcal superantigens. Sci Rep. 2019 Mar 1;9(1):3279. doi: 10.1038/s41598-019-39890-z. PMID: 30824769; PMCID: PMC6397225.

https://pubmed.ncbi.nlm.nih.gov/30824769/

Kailasan S, Kort T, Mukherjee I, Liao GC, Kanipakala T, Williston N, Ganjbaksh N, Venkatasubramaniam A, Holtsberg FW, Karauzum H, Adhikari RP, Aman MJ. Rational Design of Toxoid Vaccine Candidates for Staphylococcus aureus Leukocidin AB (LukAB). Toxins (Basel). 2019 Jun 14;11(6):339. doi: 10.3390/toxins11060339. PMID: 31207937; PMCID: PMC6628420.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628420/

Nipah vaccine

In collaboration with University of Texas Medical Branch (UTMB), AbVacc is developing a recombinant vesicular stomatitis virus (VSV)-based vaccine against Nipah virus (NiV), which causes febrile encephalitis and severe respiratory disease in humans with a fatality rate as high as 60-100% in human outbreaks (Malaysia, Bangladesh).

Pre-clinical work showed protection by vaccine lead candidate with a single dose against more pathogenic NiVB (Bangladesh) strain in rodent disease model. AbVacc is currently developing a manufacturing stable cell line for production of the VSV-based NiVB vaccine, which will be further evaluated in nonhuman primate disease model. This work is currently supported by NIH.

NiV is classified as a BSL-4 pathogen because of the high mortality rates associated with infection, the lack of effective medical countermeasures, and the ease of transmission. Additionally, it was also included in WHO’s 2018 List of Priority Pathogens for possible concern of misuse and by CDC as a Tier 1 Select Agent due to rising concerns with respiratory pathogens post COVID-19.

Related Publications:

Geisbert JB, Borisevich V, Prasad AN, Agans KN, Foster SL, Deer DJ, Cross RW, Mire CE, Geisbert TW, Fenton KA. An Intranasal Exposure Model of Lethal Nipah Virus Infection in African Green Monkeys. J Infect Dis. 2020 May 11;221(Suppl 4):S414-S418. doi: 10.1093/infdis/jiz391. PMID: 31665362; PMCID: PMC7213566.

https://pubmed.ncbi.nlm.nih.gov/31665362/

Filovirus vaccine

Using structure-based rational design, AbVacc is developing a pan-filovirus vaccine against hemorrhagic fevers caused by viruses such as Ebola, Sudan, Bundibugyo, and Marburg. Over the past several years, AbVacc and others have identified several broadly neutralizing antibodies against the filovirus glycoprotein. Using the epitope information, AbVacc has set up an iterative design building process to develop and identify a lead pan-filovirus vaccine candidate which shows protection in rodent and nonhuman primate filovirus disease models. AbVacc is in the lead optimization stage for this project.

The 2014 West African Ebola epidemic has caused over 11,000 deaths. The only approved vaccine is specific to the Zaire species of Ebola, while there are additional species of Ebola as well as the related Marburg virus that can cause fatal disease in humans. Considering the unpredictable nature of future filovirus outbreaks, the development of a pan-filovirus vaccine that would broadly protect against multiple filoviruses is critically important.

Our collaborators include The Scripps Research Institute, La Jolla Institute for Immunology, Integral Molecular, USAMRIID, and NEIDL.

Related Publications:

Zhao, Xuelian et al. “Immunization-Elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability.” Cell vol. 169,5 (2017): 891-904.e15. doi:10.1016/j.cell.2017.04.038

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803079/

Howell, Katie et al. “Cooperativity Enables Non-neutralizing Antibodies to Neutralize Ebolavirus.” Cell Rep. 2017 Apr 11; 19(2): 413–424. doi: 10.1016/j.celrep.2017.03.049

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082427/

Brannan, J.M., He, S., Howell, K.A. et al. Post-exposure immunotherapy for two ebolaviruses and Marburg virus in nonhuman primates. Nat Commun 10, 105 (2019).

https://doi.org/10.1038/s41467-018-08040-w